Process of manufacturing diphenylsulphone derivatives and product obtainable by suchprocess



Patented Nov. 2, 1943 PROCESS 'OF MANUFACTURING DIPH-ENYL- SULPHONE DERIVATIVES AND PRODUCT OBTAINABLE BY SUCH PROCESS- Paul Piihls and Fritz Mietzsch, Wuppertal-Elberheld, and Alfred Rohm, Leverkusen-I. -G.-Werk, Germany, assignors to Winthrop Chemical Company, Inc., New York, N. Y., a corporation of New York .No Drawing. Application'September 13, 1940, Serial No. 356,653. In Germany September 4,

7 Claims.

This invention relates to a process of manufacturing diphenylsulphone derivatives and to certain products obtainable by such process.

Application'for Letters Patent Ser. No. 274,228, filed May 17, 1939, now U. S. Patent 2,297,024, refers to diphenylsulphone derivatives which are substituted in the 4- and 4'-position by urea groups the one nitrogen atom of which is connected with an organic radical containing a water-solubilizing group. vThe said compounds are obtainable, for instance, by .reacting a diphenylsu'lphone-4A'-diu-rethane with an organic compound containing-apart froman amino group at least one water-solubilizing group or viceversa by reactingthe urethane derivatives of an organic compound containing a water-solubilizing group with 4,4-diaminodiphenylsulphone.

II. S. application for Letters Patent Ser. No. 304,177, filed November 13, 1939, .now U. S. Patent 2,288,422, and U. S. Patent 2,226,835 .describe particularly favorable processes for the manufacture of unsymmetrical urea. compounds by reacting organic amines with urethane compounds while using the urethane in the form of an aryl ester, i. e. in the form of carbamic acid arylesters.

In accordance with the present invention, the

said process of the copending application Ser. No.

304,177 and U. S. P. 2,226,835 may also advantageously be used in the manufacture of the urea compounds of the kind specified in application Ser. No. 274,228. Accordingly, diphenylsulphone urea derivatives are obtained by reacting 'a compound of the formula R-NH-X with a compound of the formula in which formulae R stands for an organic'radicallcon'taining a water-solubilizi'ng group selected from the group consisting of the radicals of aliphatic .po'lyhydroxy compounds derived from sugars and of aliphatic, aromatic and heterocyclic' carboxylic, sulphonic and sulp'hinic acids including those radicals which contain as an interrupting group one of the carbonamide and urea groups, and the substituents X-and Y mutually stand for hydrogen and the group -.COO- aryl. Thus, for instance, diphenylsulphone-4,4- bis-(carbamic acid arylesters) are reacted with an organiccomp'ound containing apart from an amino group at least one water-'solub ilizing group such as carboxylic, sulphonic and sulphinic acid benzene stricted thereto:

groups or a plurality of al ip'hatically bound hydroxyl groups as are contained in sugars. As such organic amino compounds containing .a water-sol ubil izi-ng group, for instance, aminoalkylor aminoarylalkyl-carboxylic acidssuch as g lycoco'l' l and aminophenyl acetic acids, aminoalky'l suip'hon ic acids such as taur ine, .aminoaryl carboxy-l im, sulp'honicor sulphinic acids such as the aminobenzene carboxylic acids, amine sill-phonic acids, aminonaphthalene sulphonic acids, aminobenzene sulphinic acids, aminoquinoli-ne sulphonic' acids and nuclear substitution products of these compounds and amino derivatives of polyvalent alcohols may be used.

' Otherwise, carbamic acid arylesters, the nitrogen atomof which is substituted. by an organic radical containing a water-solubilizing group of the kind specified above, can be reacted with 4,4"-diaminodiphenylsulphone. The carbamic acid arylesters may contain as and radicals .the radical of the various phenols and naphthols'. The reaction advantageously is performed with-heating and in the presence of .a solvent eor diluent such as water or organic solvents which are miscible with water, for instance acetone, methyl-ethyl ketone, diethyl ketone, .dioxane, tetrahydrofurane and'the like.

The inventionis furthermore"illustrated by the following examples without, however, being re- Erample 1..

2.4.8 grams of 4,='-diami-nodiphenylsulphone are suspended in 150 ccrns. zofrdioxane. 25 grams of vd-imethylaniline are added thereto and 32 grams. of chloroiormic acid .phenylester are slowly dropped .in while stirring. 'Ifhe temperature .rises :to almost 60 C. and the l,l"-diaminodiphenylsulphoner dissolves. After heating for halfan hour :on .the waterbath 52.6 grams oi 2-.napthylamin'e 6esulphonic :acid, dissolved in 400 coins. of 2% sodium hydroxide solution, are added to the .mixture containing the diphenylsulphone-i lA-carbamic acid phenylester for-med. The solution is standardized 'zaS usualito a pH, of 7.5. After 5 hours boiling While stirring the dipheny1sulphone-4A'-carb-amic acid pheny'lester which has separated dissolves. The'clear solution is madeslightly alkaline and the .dimethylaniline is blown ofi with steam. The solution is then acidified With glacial acetic acid and the phenol is removed with steam. The remaining solution is added to 1000 coins. 'o2 a"35% sodium chloride solution while stirring and the ibis- N- ('6' soldium-naphthalenesulphonate-'2) -.carlbamido- N- phenyl-fl-sulphone separated is sucked off and dried in the exsiccator. It has the fol- When reacting 2-naphthylamine-5 sulphonic-- acid, Z-naphthylamine-8-sulphonic acid and. 2-naphthylamine-7-sulphonic acid with diphen ylsulphone-4,4-di-(carbamic acid phenylester). in the same manner, the corresponding watersoluble urea compounds are obtained.

Example 2 24.8 grams of 4,4-diaminodiphenylsulphone are suspended in 150 ccms. of dioxane. grams of dimethylaniline are added and 32 grams of chloroformic acid phenylester are slowly dropped in while stirring. After heating for half an hour on the waterbath, 66 grams of the mono-sodium salt of naphthylamin'e-3,6-disulphonic acid, dissolved in 400 ccms. of a 2% sodium hydroxide solution, are added. Thenthe solution is standardized to apI-I of 7.5. After 15 hours boiling and stirring the diphenylsulphone-4A'-carbamic acid phenylester precipitated dissolves. The clear solution obtained is freed from dimethylaniline and phenol as described in Example 1 and concentrated under reduced pressure. Then, the bis-[N-(3,6 sodium-naphthalene disulphonate 2') -carbamido'-Nephenyl-4-]-sulphone being soluble in water crystallizes in the cold. It has the following formula:

NH.C 0 .NHC SOz NaOaS- S OaNa J2 By reacting sodium-Lnaphthylamine-4-sul-V phonate' and sodium-sulphanilate with vdiphenylsulphone-4,4'-dicarbamic acid phenylesterin the same manner, the corresponding urea compounds are obtained. f 1

. xExampZeJi m 48.8 grams of diphenylsulphone-4,4C-bis-carbamic acid phenylester are suspended in 200 ccms. of dioxane'. A solution of 36.2 grams of 1 aminobenzene 3,5 dicarboxylic acid and 16 grams of sodium hydroxide in 200'ccms. of water is added. This mixture is standardized to a pH of 7.5 by adding primary sodium phosphate and boiled under reflux while stirring. After 2 hours stirring the diphenylsulphone-4,4'-biscarbamic acid phenylester has dissolved. A test portion of the solution gives no precipitate when water is added. The solution is, filtered while hot with animal charcoal. The filtrate isacidified with dilute hydrochloric acid after cooling and the bis- [N' (3',5'-dicarboxy-phenyl) -carbamido-N-phenyl-4l-sulphone is sucked off, washed with water and dried at 100 C. It melts at 240 C. with decomposition. The product has the following formula:

acetone, 175 grams ofpyridine and 314 grams of chloroformic acid phenyl ester. The diphenylsulphone-4,4- biscarbamic acid phenylester separates from the mixture.

Example 4 18 grams of N-methylglucamine are dissolved in 200 ccms.;of water. 22.6 grams of diphenylsulphone-4,4"-bis-carbamic acid phenylester and 150 ccms. of dioxane are added and the mixture is boiled under reflux while stirring. After boiling for one and a half hours the diphenylsulphone-4,4-bis-carboxy1ic acid phenylester has dissolved: 'I'he solution is filtered with animal charcoal while hot and the filtrate is evaporated under reduced pressure. The glass-like solidifying residue is dissolved in methanol and the solution is boiled for a short time with animal charcoal, filtered and evaporated under reduced pressure. The bis-[N'-(1',2,3,4',5'-pentahydroxy; hexyl-6-) N' 1 methyl carbamido N phenylg4l-sulphone is soluble in water. It; has the following formula:

48.8 grams of diphenylsulphone-4,4'-bis-carbamic acid phenylester and ccms. of dioxane are added to a solution of 31.4 grams of 4-aminobenzenesulphinic acid in a solution of Sgrams of sodium hydroxide in 200 ccms. of water. The mixture is standardized with primary sodium phosphate to a pH of 7.5 and boiled under reflux while stirring. 7 After 5 hours boiling the diphenylsulphone-4,4' -bis(carbamic acid phenylester) is. dissolved. Thesolution is acidified with dilute hydrochloric acid after filtering with animal charcoal in the cold. The bis- [N'-(phenyl- 4'-sulphinic acid) -carbamido-N-phenyl-4]-sulphone separated is sucked off, washed with water and dried atxl00 C. It is soluble in dilute sodium carbonate solution. The product has the following formula: e

.[HOiS-QNH. o o .NH-O s Oi 7 Example 6' 15 grams of aminoacetic acid are dissolved in 200ccms. of water and mixed with 8 grams of sodium hydroxide. The solution is standardized to a pH of 7.5 by adding primary sodium phosphate. 48.8 grams of diphenylsulphone-4,4'-biscarbamic acid phenylester and 150 ccms. of dioxane are added and the mixture is boiled for 4 hours under reflux. The diphenylsulphone-4,4-.

. E OOQOHi YHbo NH-OL SOQ Bramble? 1 2.2.3 .:grams f 2-naphthylamine 6;sulphonic acid are dissolved in a. solution of 4'. grams of ageeagaaa' sulph onate' in! part precipitatesz. 112:4 grams. of Y 4ge-diamihodiphenylsulphome and 200 coins; of; dioxane are added, The mixture is boilediundert reflux while stirring, untilthe 4,4'-diaminodiphenylsulphone has disappeared after about hours. The clear solution is filtered with animal charcoal while hotand thefiltrate: is added after cooling to a 35% sodium chloride so'li'ition' while stirring. Thereupon, the bis-[N'-(6'-sodium'-- naphthalenesulphonate 2- l c at bamid o N phenyl-41-sulphone precipitates. It is sucked off and driedi The product has the. following Example 8 [Na OaS- 45.5 grams of the mono-sodium salt of the- 2 ('3' aminobenzoylamino')" naphthalene 3.6-

disulphonic acid are dissolved in 300 ccms. of

water and 4 grams of sodium hydroxide; grams of. diphenylsulphone-4,4'-bis-carbamic acid phenylester and 200 ccms. of dioxarre are added. The mixture: is standardized to a pH o'f 7.5 by adding primary sodium phosphate and boiled under reflux-while stirring. After 6 hours boiling a test portion of this mixture gives no precipitate when diluted with water. The clear solution is filtered with animal charcoal while. hot. chloride solution after cooling while. stirring. Thereupon, the tetra-sodiumsaltl of the sulphone-bis {2F [3- (4 phenylcarhamid'o) benzamino]-naphthalenedisulphonic acid-(3,6 precipitates" It is sucked oft and dried at 100 6. The product has" the following formula:

- {NH-410' 1 NH-.(10:.NH-- so NaOiS SOaNa The monosodium. salt of the 2-(3'-aminobenzoylamino) -naphthalene-3,6-disulphonic acid used as starting material is obtained as follows:

36.5 grams of the mono-sodium salt of the 2-naphthylamine-3,6-disulphonic acid are dissolved in 250 ccms. of water and 4 grams of sodium hydroxide, grams of sodium acetate are added and 36.5 grams of m-nitrobenzoylchloride are introduced at a temperature of 30- C. After a short time the sodium salt of the 2 (3'- nitrobenzoylamino) naphthalene 3,6-disulphonic acid crystallizes. It is sucked off, dissolved in hot water and this solution is dropped into a boiling mixture of 500 grams of iron, 1000 ccms. of water and 10 ccms. of glacial acetic acid while stirring. After 5 hours boiling the reaction solution is made alkaline with potassium carbonate, filtered while hot with animal charcoal and the filtrate is mixed after cooling with a large quantity of hydrochloric acid. Thereupon the mono-sodium salt of the 2.-(3'-amino- The filtrate is added to a 35% sodium benzoylamino)-naphthalenee36-disulfonic acid precipitates. in crystals.

In the same manner,. the 2 (4" -aminobenzoylamino'Y-naphthalene-3;6-disulionic acid is produced and reacted with. diphenylsu1phone-4L4""- biscarb amic a'cidphenyle'ster' to the tetra-sodium salt of the sulphone-bis-{2 [4' (4""-phenyrcarb'amido)" benzaminol naphthalene d 1 surphonic acid-(3,6)}.

Example 9* 35.7 gra s of N (2 naphthyl d-sulphonic"- a hid-N ni=amino phenyl5 urea are dissolved in 300* ccms. of water" and 4 grams of sodiumhydroxide; 25 grams of diphenylsulphone=4,4"- bis carbamic' a'ci'd phenylester" and 200" ccms. 0f" dioxan'e are added Themixtureisstandardi'zed to a pH of 25* by ad-dihgprimarysodium phosphate and boiled under reflux while stirring. After 3 hours"hoiling the diphenylsulphone-4,4- bis=-carbamic acidphenyl'e'st'en is dissolved. The solution is filtered while hot with animal charcoal and the filtrate is concentrated underreduced pressure. After cooling the concentrate is adde'd to a 35% sodium chloride solution while stirring. The di-sodi'um salt of the sulphonebis-{2 .E3"-(4! phenyl-carbamino) phenyl car'- bamino '-naphthalenesulphonic a'cid- (6) which has precipitated is sucked. off; pre'ssedofi and dried at C; It is easily'soluble in cold" water. The, product has the following, formula:

, The N (2 naphthyl 6-sulphonic acidi -N (maminophenyDurea employed as startingmaterial is produced. as follows:

55.2: grams. ofi m-nitraniline are dissolved in 300 ccms. of acetone, 35- grams of: pyridine. are added and 62.8 grams of chloroformic acid phenylester are dropped thereto while stirring and boiling under reflux... After 3 hours boiling the acetone solution. is pouredintowater w-hile stirring The, m -nitrophenyl-carbamic acid phenylester precipitates in crystals. It is-sucked off, washed with water and dried at 1 00 C. It melts above 260 C.

52.6- grams: of 2-naphthylamine-6-sulphonic acid are dissolved in 600: ccms. of Waterand 8- grams of sodium hydroxide while heating 51-..6 grams of m-nitrophenylcarbamic acid phenylester and 300 ccms. of, dioxane are added. The mixture is standardizedtoa pH of 7.5 by adding primary-sodiumphosphate andlboiled under reflux while stirring. After 4 hours boiling the carbamic acid phenylester has dissolved. The clear hot solution is dropped into a boiling mixture of 500 grams of iron, 1000 ccms. of water and 10 ccms. of glacial acetic acid while stirring. After 4 hours boiling the reaction mixture is made alkaline with potassium carbonate and filtered with animal charcoal while hot. The filtrate is acidified with dilute hydrochloric acid after cooling and the N -(2-naphthyl-6-sulphonic acid )-N -(m-aminopheny1) -urea which has precipitated in crystals is sucked 011 and dried at 100 C.

The N (2-naphthyl-6-sulphonic acid) -N (paminophenyl) -urea is produced in the same manner and reacted with diphenylsulphone-4,4'-biscarbamic acid phenylester to the di-sodium salt of the sulphone bis {21- [4'-(4-phenyl-carbamino) phenylcarbamino] naphthalene sulphonic acid-(6) Example 26.5 grams of 2-naphthylamineefi sulphonicacid'are dissolved in 300 ccms. of water with the addition of 4 grams of -sodium hydroxide while heating. .9.4 grams of diphenylsulphone-4,4'- bisJcarbamic acid-fi-naphthylester) and 150 ccms; of dioxane are addedl The mixture is standardized to a pH of 7.5 by adding primary sodium phosphate and boiled under reflux while stirring. After 30 hour'sstirring and boiling the bis-icarbamic acid-p-naphthylester) has dissolved. 'Thereaction solution is concentrated underlreduced pressure'land filtered from the precipitated-B naphthol while hot. The bis- [N'- (6? -,sodium' naphthalenesulphonate 2) car bam'ido-N-phenyl-ll -sulphone already mentioned inExample 1 crystallizes from the filtrate upon cooling. It has the following formula:

The diphenylsulphone-4A'bis-(carbamic acid-.

fl-naphthylester) used as starting material isobtained by 2 hours boiling of a mixture of 24.8

compound of the formula in which R represents a member of the group consisting of carboxy a1kyl,carboxy aryl, sulphonica'lkyl, su1pnonm aryl, sulphinic alkyl and sulphinic aryl; X represents hydrogen and Y represents COOaryl. a

2. The process 'which comprises reacting a compound of the formula RrNI-IX with a compound of the formula in which'R. represents a sulphonic aryl, X representshydrogen and X represents COO-aryl.

*3; Thelprocesswhich comprises reacting a compound of the, formula R--NHX with a comp oundo'fthe formula in which R. representsja member of the group consisting of ,carboxy alkyl, carboxy aryl, sulphonic alkyLsulphonic aryl, sulphinic alkyl and sulphinic aryl; X represents hydrogen and Y represents -=COO-.phenyl.

' 4; Theprocess which comprises reacting a compound of the formula R'-NH-X with a compound of the formula 0 s NH-Y I inwhich It represents a sulphonic naphthyl, X represents hydrogen and Y represents COO /5.' A compound of the formula wherein stands for one of the groups CONH and NHCONH and n stands for one of the numbers 1 and 2,- and its alkali and alkaline eartlrmetal salts, which are soluble in" water with neutral reaction;

"7. Acompound having the formula NH-C o NHIG O.NH- SOz and water soluble alkali and alkaline earth metal salts thereof,

" PAUL Poms.

FRITZ MIETZSCH. ALFRED ROHM. 

